The present invention relates to cis-oxalato(trans-1-1,2-cyclohexanediamine) Pt(II) complex having high optical purity which may be employed as starting material of carcinostatic substance and a process of preparing same.
Trans-1-1,2-cyclohexanediamine can be obtained by reacting trans-dl-1,2-cyclohexanediamine with tartaric acid to form diastereomers and optically resoluting the respective diastereomers by means of a recrystallization method utilizing the difference of solubilities of the respective diastereomers. However, this method possesses a limitation because the solubility difference is not large so that it is reported that optical purity of 99.5 % or more cannot be industrially attained.
Accordingly, in order to obtain a platinum complex represented by Formula 1 having high optical purity, after the resolution of cis-trans stereoisomers of 1,2-cyclohexanediamine which is starting material for the preparation of the platinum complex in accordance with a resolution refining process ##STR2## (Japanese patent publication No.61-4827), the optical resolution of the trans isomer is conducted by, in accordance with a normal process, forming a diastereomer by means of tartaric acid followed by its recrystallization. A platinum complex prepared by employing this resoluted isomer is further optically resoluted by means of high performance liquid chromatography (hereinafter referred to as "HPLC method") to produce the platinum complex (Formula 1) having the high optical purity (U.S. patent application Ser. No. 08/043,901 and European patent application No.93830160.3). The optical resolution of the final product is conventionally required because the resolution and refining of the trans-1-1,2-cyclohexanediamine is insufficient. Since the trans-1-1,2-cyclohexanadiamine is the important starting material of cis-oxalato(trans-1-1,2-cyclohexanadiamine) Pt(II) complex which is the starting material of a carcinostatic agent, the trans-1-1,2-cyclohexanediamine having stably higher optical purity has been required.
The platinum complex (Formula 1) has been synthesized in accordance with a preparation process shown as the below equation (Formula 2).
Many optically active pharmaceuticals may have a considerable difference in carcinostatic activities and their side effects due to their isomerism so ##STR3## that their optical purity is important when they are utilized as the pharmaceuticals.